Domain swapping is a consequence of minimal frustration

Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13786-91. doi: 10.1073/pnas.0403724101. Epub 2004 Sep 10.

Abstract

The same energy landscape principles associated with the folding of proteins into their monomeric conformations should also describe how these proteins oligomerize into domain-swapped conformations. We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein, both of whose monomeric and domain-swapped structures have been solved. The model, which we call the symmetrized Gō-type model, incorporates only information regarding the monomeric conformation in an energy function for the dimer to predict the domain-swapped conformation. A striking preference for the correct domain-swapped structure was observed, indicating that overall monomer topology is a main determinant of the structure of domain-swapped dimers. Furthermore, we explore the free energy surface for domain swapping by using our model to characterize the mechanism of oligomerization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Models, Theoretical
  • Protein Conformation
  • Protein Folding*
  • Proteins / chemistry*
  • Proteins / metabolism*

Substances

  • Proteins